Sulforaphane is a substance that is released when broccoli is eaten. It has been studied extensively in the laboratory and has been shown to improve outcome after SAH in animals. However on its own SFN has a short shelf life and is not practical for clinical use. When synthetic SFN is mixed with cyclodextrin it forms SFX-01. SFX-01 is stable and on ingestion releases SFN.

This study will assess if SFX-01 is safe, gets into the brain and reduces the inflammation after SAH.It will randomise 90 patients who have suffered a severe SAH in the last 48 hours to receive either SFX-01 or placebo tablets for 28 days. They will be monitored closely with blood and cerebrospinal fluid samples and ultrasound recordings while in hospital and will be followed up at 28 days, 3 months and 6 months with assessments of their outcome. They will also have an MRI at 6 months. By the end of this study we will have assessed the safety and tolerability of SFX-01, established how much and how quickly it gets into the brain and have an estimate of how much of a difference it makes to patient outcome. This will allow us to design a future study to definitively ascertain is usefulness in SAH patients

Summary
This is a Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of SFX-01 in Subarachnoid Haemorrhage, with exploratory evaluations of efficacy.
Research Details

The study is a randomised, double-blind, parallel-group design comparing SFX-01 (300 mg) taken orally as capsules or as a suspension via a nasogastric tube (NG) twice-daily for up to 28 days versus placebo in 90 patients who have had SAH and present within 48 hours of ictus.

Subjects will receive SFX-01/Placebo in order to review potential outcomes investigating the long-term complications of SAH such as Delayed Cerebral Ischaemia, as reflected by Trans-Cranial Doppler (TCD) readings. The objective is to demonstrate safety and search for signals of efficacy in patients that have had SAH.

A sub-study will be conducted in up to 12 patients where an External Ventricular Drain (EVD) fitted; serial CSF samples will be taken pre- & post-dose on two occasions to determine pharmacokinetics of Sulforaphane in CSF in comparison with plasma pharmacokinetics. Sub-study patients will undergo all other procedures (with the exception of lumbar puncture).

Treatment duration is up to 28 days; follow up duration is 28 days, three and six months. The planned trial period is 24 months.

Phase
Phase 2
Study Type
Interventional
Intervention
Drug : SFX-01, Drug : Placebo

Study Arm Groups : SFX-01, Placebo

Primary Outcome Measures
Number of participants with treatment-related adverse events as assessed by Common Toxicity Criteria; up to 28 days; Maximum CSF Concentration [Cmax],; up to 28 days; Number of participants with treatment related reduction in middle cerebral artery (MCA) peak flow velocity following Subarachnoid Haemorrhage (SAH) measured by trans cranial doppler ultrasound; up to 28 days
Secondary Outcome Measures
modified Rankin Scale; up to 180 days post ictus; Plasma PK; up to 28 days; CSF drug levels; up to 14 days; Serum Haptoglobin levels; Up to 28 days; Delayed Cerebral Ischaemia; Up to 28 days